1. Renal Replacement and Fluid Overload Therapies
The term “Renal Replacement Therapy” (RRT) generally refers to all forms of dialysis, solute and fluid balancing therapy. Renal replacement therapy performs two primary functions: ultrafiltration (removal of water from blood plasma), and solute clearance (removal of different molecular weight solid substances from blood plasma). The filter, also called hemofilter or “dialyzer”, used in RRT may perform either or both of these functions simultaneously, with or without fluid replacement. Various modes of renal replacement therapy relate to whether fluids, solutes or both are removed by the filter and whether fluids are replaced into the filtered blood. “Clearance” describes the removal of substances, both normal and waste products, from the blood whether by normal kidney function or during renal replacement therapy.
Fluid overload therapy relates to removal of excess fluids from extracorporeal blood in patients that, for example, suffer from congestive heart failure (CHF). Patients suffering from CHF have weakened hearts that are unable to provide normal blood flow to the kidney and organs of the body. CHF patients may have normal kidneys, but lack sufficient blood flow to maintain proper kidney functions of removing excess fluid, e.g., water, from the body. The build-up of excessive fluids due to inadequate kidney functions further increases the blood pumping load on the heart, which is already suffering from CHF.
Dialysis is the diffusive transfer of small solutes out of a blood plasma compartment by diffusion across a membrane of a filter. Diffusion of the solutes occurs due to a concentration gradient across the filter membrane. Diffusion occurs from the filter compartment with higher concentration (typically the blood compartment) to the filter compartment with lower concentration (typically the dialysate compartment). Since the concentration of solutes in the plasma decreases, clearance is obtained, but fluid may not be removed. Ultrafiltration can be combined with dialysis.
Hemofiltration is the combination of ultrafiltration and fluid replacement, typically in much larger volumes than needed for fluid control. The replacement fluid contains electrolytes, but not other small molecules. Since the net effect of replacing fluid without small solutes and ultrafiltration of fluid with small solutes results in net removal of small solutes, clearance is obtained.
Ultrafiltration and hemofiltration operate primarily by convection of solutes through the filter membrane. In hemofiltration, a solute molecule is swept through a filter membrane by a moving stream of ultrafiltrate. Proteins and blood cells are retained in the blood by the membrane. In patients with renal failure, renal replacement therapy, such as hemofiltration or dialysis, removes undesired solutes from their blood. In renal replacement therapy, vital elements such as electrolytes are also removed from the blood and need to be replaced to maintain electrolyte balance. Thus, hemofiltration and dialysis treatments usually require fluid replacement. In contrast, ultrafiltration does not remove substantial amounts of electrolytes and solutes.
Hemodialysis requires a large filter membrane surface to enable effective solute clearance by diffusion. Hemofiltration requires large amounts of ultrafiltrate to be transferred across the membrane to remove a relatively small amount of solute. Large amounts of fluid such as 1 to 4 liters per hour (L/hour) are continuously being removed during continuous veno-venous hemofiltration (CVVH). The resulting loss of water and electrolytes are immediately dangerous to the patient. To maintain fluid and electrolyte balance, an equally large or slightly lower amount of replacement fluid is infused into the patient. Replacement fluid is thus added into the extracorporeal blood circuit before or after the filter.
Ultrafiltration utilizes extracorporeal blood filters to remove fluids from blood, where the filter generally includes a blood passage having input and output ports, a filtered fluid discharge port and a finely porous membrane separating the blood passage and the ultrafiltrate of filtrate discharge port. The ultrafiltrate output from the filter is substantially all fluids, e.g., water, and is relatively free of solutes.
Different modalities of Continuous Renal Replacement Therapy (CRRT) have been used to treat patients suffering from excess fluid overload and acute renal failure. In the acute condition, CRRT has been performed using standard methods of hemodialysis and continuous arterio-venous hemofiltration (CAVH). More recently, CVVH has been used to reduce the complications associated with such issues as hemodynamic instability and need for arterial access.
2. Limitations of Existing Blood Devices
Extracorporeal blood treatment usually requires anticoagulation of blood to avoid blood clots forming the in blood circuit. Blood coagulation is typically activated by shear and by the contact of blood to the artificial surface of the extracorporeal circuit. Blood does not clot until several minutes after the activation of the clotting system. Reducing the residence time of blood in a blood circuit can allow the blood to flow through the circuit and back into the blood stream of the patient before a clot forms. Once the blood is returned to the natural circulatory system of the patient, the blood clotting activation process stops. Accordingly, delays in the movement of blood through the extracorporeal blood circuit may allow the clotting activation process sufficient time within which to form a clot.
FIGS. 10, 11, 12 and 13 are enlarged cross-sectional views of conventional filter headers 511, 512 and 513 such as sold under the trade names Gambro FH22H™, Cobe M60™ and Fresenius F80™. The filter header cap 512 (See, e.g., U.S. Pat. No. 4,990,251) has a separate polymer seal ring 532 forming a face seal between the rim 531 of the potting compound and the filter header cap 533. The rim is an annular ring of potting compound that is devoid of hollow fiber filters and is impervious to blood. Blood that flows to the gap between the rim 531 and cap 533 eddies just inside the circumference of the seal ring 532 and tends to clot at the seal ring. A conventional filter header cap 511 such as the Cobe M60™ has a sealing tooth 530 instead of the sealing ring of the header cap 512.
Sealing rings and teeth are not employed in some conventional filter headers 513, e.g., the Gambro FH22H™. The filter header cap 513 has a filter header cap 535 that is welded or bonded to the outer perimeter of the cylindrical filter case 536. As is shown in FIG. 11, which is an enlargement of the region 11 in FIG. 10, a wide annular dead zone 538 exists between the cap and the rim formed by the end of the filter case 536 and the rim of impervious potting compound 537. Blood clots tend to form in dead zones. The conventional filter headers shown in FIGS. 10 to 13 each have significant dead zone areas 538, which typically have a width of 2.54 mm to 5.08 mm (0.10 to 0.20 inches). These dead zones result in the stagnation of blood and promote the formation of blood clots.
FIG. 14 is a graph of simulated streamlines of the blood flow through a conventional filter header cap have a wide dead zone 538. The streamlines were generated by Computational Fluid Dynamics that predict the flow streamlines within various filter cap flow paths. Smooth stream lines of blood 540 show the blood passing through the filter header cap and into the open hollow fibers of the filter. Smooth stream lines suggest the absence of dead zones, flow eddies and recirculation. However, the dead zones 538 at the potting compound rims result in recirculation areas 541 (FIG. 14) of the blood flow.
Delays in the blood circuit occur if the fluid path contains poorly perfused dead zones where blood stagnates for a long period, such as in eddy pools and at flow blockages that force the blood to recirculate through a portion of the passage. A common location for dead zones is in the entrance header cap of a filter, where the blood flows from narrow blood tubes towards the relatively wide entrance of a fiber bundle. The fiber bundles are typically encircled by annular rims of potting compound. These impervious rims are at the outer periphery of the header cap and at the side-wall of the filter housing. These rims form dead zones in the blood flow. The rims block the flow of blood and cause the blood to stagnate and recirculate in eddy currents in the filter header cap. Blood clots tend to form in the dead zones. The clots eventually will block the filter and entire circuit.